What are the risks of consuming cannabis products for symptom management while receiving immunotherapy for cancer? — Name withheld on request

With an increasing number of states legalizing medicinal and/or recreational marijuana and related products, more and more people with cancer are using these products. As of this writing, the US Drug Enforcement Agency lists marijuana and its cannabinoids as a Schedule I controlled substance that cannot be sold, prescribed, or possessed under federal law.1 Rates of cannabis use among cancer patients varies in studies, likely due to its current federal designation, and ranges from 24% (current use) to more than 40% (ever use). 

Patients should be encouraged to report use of cannabis and any other complementary and alternative medicine products so potential interactions with cancer therapy can be identified. This is especially important with the immune checkpoint inhibitors, including CTLA-4 antibodies (ipilimumab [Yervoy]), PD-1 inhibitors (eg, nivolumab [Opdivo]) and PDL-1 inhibitors (eg, durvalumab [Imfinzi]). 

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Use of immune checkpoint inhibitors in cancer is continually increasing, both as single agent therapy and in combination with cytotoxic chemotherapy (eg, carboplatin [Paraplatin]; pemetrexed [Alimta]) or targeted agents (tyrosine kinase inhibitors such as axitinib [Inlyta] and others). Multiple analyses have shown that concurrent use of cannabis products with immune checkpoint inhibitors is associated with reduced treatment efficacy. 

In a retrospective, single-center review of 104 patients with advanced cancer, overall survival was reduced in the 27% of patients who used cannabis concurrently with their immune checkpoint inhibitor compared with those who did not use cannabis (16 vs 40 months).2 This trial included prescription cannabinoids such as dronabinol (Marinol) as well as marijuana use. 

Another prospective, observational study, this one with 102 patients beginning immune checkpoint inhibitors for metastatic cancer found lower rates of clinical benefit (complete response + partial response + stable disease; 39% vs 59%), shorter time to tumor progression (3.4 vs 13.1 months), and shorter overall survival (6.4 vs 28.5 months) in the 34 patients who also used cannabis.3 This analysis noted a trend toward reduced adverse effects of immunotherapy, but this was not statistically significant. 

The overall clinical literature is limited by nonrandomized, observational study design; however, these observations suggest that concurrent use of cannabis with immune checkpoint inhibitors should be discouraged until more information is available.  

The exact mechanism for this effect is unclear, although it appears that cannabinoids may have some role in immune system regulation and have anti-inflammatory activity that may dampen the response to immune checkpoint inhibitors. 

Patient information regarding the general use of cannabis in cancer is available from the American Cancer Society (“Marijuana and Cancer”) and the National Cancer Institute (“Cannabis and Cannabinoids (PDQ®) – Patient Version”). 

References 

1. Department of Justice/Drug Enforcement Administration. Drug fact sheet: marijuana/cannabis. GetSmartAboutDrugs.com. Published April 2020. Accessed September 9, 2021. https://www.dea.gov/sites/default/files/2020-06/Marijuana-Cannabis-2020_0.pdf

2. Biedny A, Szpunar S, Abdalla A, Kafri Z, Hadid TH. The effect of concomitant cannabinoids during immune checkpoint inhibitor treatment of advanced stage malignancy. J Clin Oncol. 2020;38(15_suppl):e15064. doi:10.1200/jco.2020.38.15_suppl.e15064

3. Bar-Sela G, Cohen I, Campisi-Pinto S, et al. Cannabis consumption used by cancer patients during immunotherapy correlates with poor clinical outcome. Cancers (Basel). 2020;12(9):2447. doi:10.3390/cancers12092447